Schömig E, Schönfeld C L, Halbrügge T, Graefe K H, Trendelenburg U
Institut für Pharmakologie und Toxikologie der Universität Würzburg, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Aug;342(2):160-70. doi: 10.1007/BF00166959.
After loading of the incubated rat vas deferens with 0.2 mumol/l 3H-noradrenaline (followed by 100 min of wash-out with amine-free solution), the efflux of endogenous and exogenous compounds was determined by HPLC with electrochemical detection and by column chromatography with scintillation counting. Two different types of heterogeneity of labelling were found. The first one is due to the preferential labelling of varicosities close to the surface of the tissue, the second one to the preferential labelling of vesicles close to the surface of loaded varicosities. As diffusion distances within the tissue and within varicosities are then longer for endogenous than for exogenous amine and metabolites, the composition of spontaneous efflux of exogenous compounds differed from that for endogenous compounds. Because of preferential neuronal and vesicular re-uptake of endogenous noradrenaline, the percentage contribution by noradrenaline to overall efflux was: endogenous less than exogenous. While 3H-DOPEG was the predominant exogenous metabolite, DOPEG and MOPEG equally contributed to the "endogenous" efflux. Desipramine abolished the consequences of the first heterogeneity of labelling, i.e., it increased the efflux more for endogenous than for exogenous noradrenaline; moreover it decreased the efflux of 3H-DOPEG, but increased that of 3H-MOPEG. The reserpine-like compound Ro 4-1284, on the other hand, abolished the consequences of the second type of heterogeneity; it reduced the specific activity of "total efflux" (i.e., of the sum of noradrenaline + DOPEG + MOPEG) to the specific activity of the tissue noradrenaline. The degree of heterogeneity of labelling was reduced after inhibition of monoamine oxidase and also when the tissues were loaded with 2 or 20 mumol/l 3H-noradrenaline. It is proposed that the various "compartments" and "pools" of noradrenaline described in the literature reflect the two heterogeneities described here.
用0.2 μmol/L的3H-去甲肾上腺素孵育大鼠输精管后（随后用无胺溶液洗脱100分钟），通过高效液相色谱-电化学检测法和柱色谱-闪烁计数法测定内源性和外源性化合物的流出量。发现了两种不同类型的标记异质性。第一种是由于靠近组织表面的曲张体优先被标记，第二种是由于靠近负载曲张体表面的囊泡优先被标记。由于组织内和曲张体内内源性胺和代谢物的扩散距离比外源性胺和代谢物的扩散距离长，外源性化合物的自发流出成分与内源性化合物不同。由于内源性去甲肾上腺素优先被神经元和囊泡再摄取，去甲肾上腺素对总流出量的贡献百分比为：内源性小于外源性。虽然3H-DOPEG是主要的外源性代谢物，但DOPEG和MOPEG对内源性流出量的贡献相同。地昔帕明消除了第一种标记异质性的影响，即它对内源性去甲肾上腺素的流出量增加幅度大于外源性去甲肾上腺素；此外，它降低了3H-DOPEG的流出量，但增加了3H-MOPEG的流出量。另一方面，利血平样化合物Ro 4-1284消除了第二种异质性的影响；它将“总流出量”（即去甲肾上腺素+DOPEG+MOPEG的总和）的比活性降低到组织去甲肾上腺素的比活性。抑制单胺氧化酶后以及当组织用2或20 μmol/L的3H-去甲肾上腺素负载时，标记的异质性程度降低。有人提出，文献中描述的去甲肾上腺素的各种“区室”和“池”反映了这里描述的两种异质性。
